Abrir sesión | Regístrese | Contacto | English |
Resúmenes Epistemonikos
Medwave 2016;16(Suppl5):e6632 doi: 10.5867/medwave.2016.6632
¿Disminuye el riesgo cardiovascular al agregar ezetimibe al tratamiento con estatinas?
Does the addition of ezetimibe to statins reduce cardiovascular risk?
Francisca I Araya, Bruno Grassi
Referencias | Descargar PDF |
Para Descargar PDF debe Abrir sesión.
Imprimir | A(+) A(-) | Lectura fácil

Resumen

Las estatinas constituyen el pilar del tratamiento hipolipemiante en la actualidad, ya que reducen el riesgo cardiovascular, tanto en prevención primaria como secundaria. Sin embargo, sólo un tercio de los pacientes en tratamiento alcanza las metas establecidas en diversas guías clínicas y además, aunque las alcancen, mantienen un riesgo cardiovascular mayor al de la población sana. Uno de los nuevos hipolipemiantes es el ezetimibe. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en múltiples bases de datos, identificamos nueve revisiones sistemáticas que en conjunto incluyen 67 estudios aleatorizados. Realizamos un metanálisis y tablas de resumen de los resultados utilizando el método GRADE. Concluimos que la adición de ezetimibe al tratamiento con estatinas probablemente resulta en poca o nula diferencia en la mortalidad total, y que podría llevar a una pequeña reducción en el riesgo de infarto y accidente cerebrovascular, pero la certeza de la evidencia es baja.


 
Problema

La enfermedad cardiovascular constituye la principal causa de mortalidad en población adulta. Los niveles elevados de colesterol LDL se asocian a mayor riesgo de enfermedad coronaria, y este riesgo es menor con niveles más bajos hasta llegar a un nivel de aproximadamente 80 mg/dl (2,1 mmol/l) [1]. Es por esto que múltiples guías clínicas han establecido metas de LDL, y para lograrlas se requiere muchas veces un tratamiento intensivo [1]. Si bien esto puede intentarse con altas dosis de estatinas, un porcentaje sustantivo de los pacientes no logra la meta. Además, aunque se alcancen las metas deseadas, el riesgo cardiovascular de los pacientes sigue siendo mayor al de la población sana, lo que se ha denominado “riesgo residual”. Se han planteado nuevas opciones, como el ezetimibe, un inhibidor de la absorción intestinal de colesterol que bloquea la absorción de sales biliares y de colesterol proveniente de la dieta, sin afectar las vitaminas liposolubles o los triglicéridos. Considerando que su mecanismo de acción difiere del de las estatinas, las cuales inhiben la síntesis de colesterol, se ha propuesto que podrían ser una combinación efectiva. Sin embargo, no está claro si agregar ezetimibe al tratamiento con estatinas tiene beneficios, especialmente en reducir el riesgo cardiovascular a largo plazo.

Métodos

Utilizamos la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en 30 bases de datos, para identificar revisiones sistemáticas y sus estudios primarios incluidos. Con esta información generamos un resumen estructurado, siguiendo un formato preestablecido, que incluye mensajes clave, un resumen del conjunto de evidencia (presentado como matriz de evidencia en Epistemonikos), metanálisis del total de los estudios, tablas de resumen de resultados con el método GRADE, y tabla de otras consideraciones para la toma de decisión.

Mensajes clave

  • La adición de ezetimibe al tratamiento con estatinas probablemente resulta en poca o nula diferencia en la mortalidad total.
  • La adición de ezetimibe al tratamiento con estatinas podría llevar a una pequeña reducción en el riesgo de infarto y accidente cerebrovascular, pero la certeza de la evidencia es baja.
  • La adición de ezetimibe al tratamiento con estatinas no aumenta los efectos adversos serios.
Acerca del conjunto de evidencia para esta pregunta

Cuál es la evidencia. 
Véase matriz de evidencia en Epistemonikos más abajo.

Encontramos nueve revisiones sistemáticas [2], [3],
[4], [5], [6], [7], [8], [9], [10] que incluyen 67 estudios controlados aleatorizados sobre ezetimibe e hipercolesterolemia, reportados en 69 referencias
[11], [12], [13], [14], [15], [16], [17], [18], [19], [20],
[21], [22], [23], [24], [25], [26], [27], [28], [29], [30], 
[31], [32], [33], [34], [35], [36], [37], [38], [39], [40],
[41], [42], [43], [44], [45], [46], [47], [48], [49], [50],
[51], [52], [53], [54], [55], [56], [57], [58], [59], [60],
[61], [62], [63], [64], [65], [66], [67], [68], [69], [70],
[71], [72], [73], [74], [75], [76], [77], [78], [79].

Este resumen analiza los 37 estudios que compararon ezetimibe asociado a estatinas versus la monoterapia con estatinas en la misma dosis, que corresponde a la pregunta clínicamente más relevante [12], [17], [18], [19], [23], [24], [26], [27], [28], [29], [31], [34], [35], [36], [37], [40], [42], [43], [46], [48], [49], [50], [52], [53], [54], [58], [65], [66], [67], [68], [69], [71], [73], [74], [76], [77], [78].

Qué tipo de pacientes incluyeron los estudios

Nueve estudios incluyeron pacientes con enfermedad coronaria conocida [26], [27], [37], [42], [48], [53], [54], [71], [74], de los cuales dos incluyeron pacientes con niveles de LDL menor a 160 mg/dl [42], [71]; un estudio incluyó pacientes con hipercolesterolemia y riesgo cardiovascular alto [58]; un estudio fue realizado en pacientes con síndrome coronario agudo [29]; un estudio incluyó pacientes con infarto agudo al miocardio [69]; un estudio fue realizado en pacientes diabéticos con hipercolesterolemia [17]; dos estudios incluyeron pacientes con enfermedad arterial periférica [50], [76]; dos estudios fueron realizados en pacientes con enfermedad renal crónica [31], [73]; 18 estudios fueron realizados en pacientes con hipercolesterolemia primaria [12], [18], [19], [23], [24], [28], [34], [35], [36], [40], [43], [46], [65], [66], [67], [68], [77], [78] (uno centrado solo en sujetos afro-americanos [18]); un estudio incluyó pacientes con hipercolesterolemia familiar homocigota [52]; y un estudio fue realizado en sujetos sanos [49]. 

Qué tipo de intervenciones incluyeron los estudios

Cinco estudios compararon el efecto de atorvastatina y ezetimibe versus atorvastatina más placebo [26], [42], [66], [67], [74]; 22 estudios compararon el uso de simvastatina más ezetimibe versus simvastatina más placebo [17], [18], [19], [23], [28], [29], [31], [35], [37], [40], [43], [46], [49], [53], [54], [68], [69], [71], [73], [76], [77], [78]; un estudio comparó el efecto de atorvastatina y simvastatina asociado a ezetimibe versus ambas estatinas por separado más placebo [52]; un estudio comparó el efecto de simvastatina más ezetimibe versus atorvastatina más placebo [65]; seis studios compararon pravastatina, lovastatina o fluvastatina o varias estatinas dentro del mismo estudio asociado a ezetimibe versus la estatina sola [12], [24], [34], [36], [48], [58]; y dos estudios compararon rosuvastatina más ezetimibe versus rosuvastatina asociado a placebo [27], [50].

Qué tipo de desenlaces midieron

Si bien los estudios primarios reportan los desenlaces de manera diversa, la forma en que las diferentes revisiones sistemáticas identificadas los agruparon es la siguiente:

  • Mortalidad total
  • Mortalidad cardiovascular
  • Eventos cardiovasculares (infarto agudo al miocardio, accidente cerebrovascular, necesidad de reperfusión coronaria, angina inestable de alto riesgo)
  • Infarto agudo al miocardio 
Resumen de los resultados

La información sobre los efectos del ezetimibe asociado a estatinas que se analizó en este resumen, está basada en 37 estudios controlados aleatorizados [12], [17], [18], [19], [23], [24], [26], [27], [28], [29], [31], [34], [35], [36], [37], [40], [42], [43], [46], [48], [49], [50], [52], [53], [54], [58], [65], [66], [67], [68], [69], [71], [73], [74], [76], [77], [78]. Sólo nueve estudios reportaron mortalidad total [29], [31], [42], [43], [50], [66], [73], [74], [76], siete estudios analizaron infarto al miocardio no fatal [27], [29], [43], [50], [73], [74], [76], seis accidente cerebrovascular [31], [43], [50], [73], [74], [76], tres revascularización coronaria [27], [29], [74] y 17 estudios analizaron efectos adversos serios [17], [23], [24], [27], [29], [30], [31], [37], [42], [46], [53], [54], [64], [66], [71], [73], [78]. El resumen de los resultados es el siguiente:

  • La adición de ezetimibe al tratamiento con estatinas probablemente resulta en poca o nula diferencia en la mortalidad total. La certeza de la evidencia es moderada.
  • La adición de ezetimibe al tratamiento con estatinas podría llevar a una pequeña reducción en el riesgo de infarto, pero la certeza de la evidencia es baja.
  • La adición de ezetimibe al tratamiento con estatinas podría llevar a una pequeña reducción en el riesgo de accidente cerebrovascular, pero la certeza de la evidencia es baja.
  • La adición de ezetimibe al tratamiento con estatinas no aumenta los efectos adversos serios. La certeza de la evidencia es alta.

Otras consideraciones para la toma de decisión

A quién se aplica y a quién no se aplica esta evidencia
  • La mayor proporción de los datos presentados proviene de estudios con pacientes con niveles de LDL ≤ 140 mg/dl, con enfermedad renal crónica o con síndrome coronario agudo reciente.
  • En pacientes con un menor riesgo cardiovascular es razonable esperar un resultado similar, aunque si el efecto del ezetimibe fuera cierto, en estos pacientes sería aún de menor cuantía, dado que son pacientes cuyo riesgo basal es más bajo.
Sobre los desenlaces incluidos en este resumen
  • Se incluyeron los desenlaces más relevantes para la toma de decisión.
  • Es importante destacar que el nivel de colesterol LDL que se logra no constituye un desenlace importante para el paciente, sino un desenlace sustituto. Estos sólo deben ser utilizados si no existe información sobre los primeros.
  • Otro desenlace habitualmente utilizado por las principales guías es la revascularización. Este no fue incluido por ser de menor importancia relativa que los otros. De todas formas, no se observó ningún efecto sobre este desenlace (RR 0,96; IC 95% 0,90 a 1,01; certeza de la evidencia alta).
Balance riesgo/beneficio y certeza de la evidencia
  • Se trata de un tratamiento que probablemente no tiene efecto sobre la mortalidad, y que podría tener un efecto pequeño sobre el riesgo de presentar eventos cardiovasculares, aunque con evidencia de baja certeza. Pero por otra parte, no tiene efectos adversos serios. 
Qué piensan los pacientes y sus tratantes
  • Al tratarse de una intervención con un beneficio pequeño e incierto, pero sin efectos adversos y de relativo alto costo, es probable que exista gran variabilidad en la decisión tomada por distintos pacientes y tratantes, dependiendo de cuánto valor pongan estos en cada uno de estos factores.
Consideraciones de recursos
  • Dado el alto costo del ezetimibe, y la baja magnitud del beneficio es poco probable que se trate de una terapia costo-efectiva, aunque una evaluación formal de este aspecto es deseable en los escenarios en que se esté considerando su utilización.
Diferencias entre este resumen y otras fuentes
  • Este resumen concuerda parcialmente con las distintas revisiones sistemáticas, las cuales difieren entre sí. Por ejemplo, una de las revisiones concluye que a pesar de ser una diferencia pequeña, por la importancia de los desenlaces, estas no dejan de ser importantes para los pacientes [3], mientras que otras sugieren que el ezetimibe no agrega beneficio importante al tratamiento con estatinas como monoterapia [5].
  • Las guías de la European Society of Cardiology recomiendan el uso de ezetimibe en pacientes con niveles de LDL ≥70mg/dl a pesar de tener la dosis máxima tolerada de estatinas [80]. Esta recomendación no difiere de este resumen ya que recomienda ezetimibe exclusivamente frente al fracaso de tratamiento con estatinas, reconociendo la pequeña reducción en los eventos cardiovasculares y nula diferencia en mortalidad. 
¿Puede que cambie esta información en el futuro?
  • La probabilidad que futura evidencia cambie las conclusiones de este resumen es alta para algunos desenlaces críticos para la toma de decisión, debido a la incertidumbre existente.
Cómo realizamos este resumen

Mediante métodos automatizados y colaborativos recopilamos toda la evidencia relevante para la pregunta de interés y la presentamos en una matriz de evidencia.

Siga el enlace para acceder a la versión interactiva: Ezetimibe para la hipercolesterolemia

Notas

Si con posterioridad a la publicación de este resumen se publican nuevas revisiones sistemáticas sobre este tema, en la parte superior de la matriz se mostrará un aviso de “nueva evidencia”.  Si bien el proyecto contempla la actualización periódica de estos resúmenes, los usuarios están invitados a comentar en Medwave o contactar a los autores mediante correo electrónico si creen que hay evidencia que motive una actualización más rápida.

Luego de crear una cuenta en Epistemonikos, al guardar las matrices recibirá notificaciones automáticas cada vez que exista nueva evidencia que potencialmente responda a esta pregunta. El detalle de los métodos para elaborar este resumen están descritos aquí: http://dx.doi.org/10.5867/medwave.2014.06.5997.

La Fundación Epistemonikos es una organización que busca acercar la información a quienes toman decisiones en salud, mediante el uso de tecnologías. Su principal desarrollo es la base de datos Epistemonikos (www.epistemonikos.org).

Los resúmenes de evidencia siguen un riguroso proceso de revisión por pares interno.

Declaración de conflictos de intereses
Los autores declaran no tener conflictos de intereses con la materia de este artículo.

Licencia Creative Commons Esta obra de Medwave está bajo una licencia Creative Commons Atribución-NoComercial 3.0 Unported. Esta licencia permite el uso, distribución y reproducción del artículo en cualquier medio, siempre y cuando se otorgue el crédito correspondiente al autor del artículo y al medio en que se publica, en este caso, Medwave.

 

Statins are the mainstay of lipid-lowering therapy nowadays, since they reduce cardiovascular risk when used as primary or secondary prevention. However, only one third of the patients reach the goals established in several guidelines, and even if they do, they keep a risk higher than healthy controls. One of the new lipid-lowering agents is ezetimibe. Searching in Epistemonikos database, which is maintained by screening multiple databases, we identified nine systematic reviews comprising 67 trials overall. We combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded adding ezetimibe to statins probably results in little or no difference in overall mortality. It might lead to a small reduction in the risk of myocardial infarction and stroke, but the certainty of the evidence is low.

Autores: Francisca I Araya[1], Bruno Grassi[1,2]

Filiación:
[1] Proyecto Epistemonikos, Santiago, Chile
[2] Departamento de Nutrición y Diabetes, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile

E-mail: bagrassi@gmail.com

Correspondencia a:
[1] Facultad de Medicina
Pontificia Universidad Católica de Chile
Diagonal Paraguay 476
Santiago Centro
Chile

Citación: Araya FI, Grassi B. Does the addition of ezetimibe to statins reduce cardiovascular risk?. Medwave 2016;16(Suppl5):e6632 doi: 10.5867/medwave.2016.6632

Fecha de publicación: 5/12/2016

Ficha PubMed

Comentarios (0)

Nos complace que usted tenga interés en comentar uno de nuestros artículos. Su comentario será publicado inmediatamente. No obstante, Medwave se reserva el derecho a eliminarlo posteriormente si la dirección editorial considera que su comentario es: ofensivo en algún sentido, irrelevante, trivial, contiene errores de lenguaje, contiene arengas políticas, obedece a fines comerciales, contiene datos de alguna persona en particular, o sugiere cambios en el manejo de pacientes que no hayan sido publicados previamente en alguna revista con revisión por pares.

Aún no hay comentarios en este artículo.

Para comentar debe iniciar sesión

Medwave publica las vistas HTML y descargas PDF por artículo, junto con otras métricas de redes sociales.

Se puede producir un retraso de 48 horas en la actualización de las estadísticas.

  1. Chan DK, O'Rourke F, Shen Q, Mak JC, Hung WT. Meta-analysis of the cardiovascular benefits of intensive lipid lowering with statins. Acta Neurol Scand. 2011 Sep;124(3):188-95. | CrossRef | PubMed |
  2. Sharma M, Ansari MT, Abou-Setta AM, Soares-Weiser K, Ooi TC, Sears M, et al. Systematic review: comparative effectiveness and harms of combination therapy and monotherapy for dyslipidemia. Ann Intern Med. 2009 Nov 3;151(9):622-30. | CrossRef | PubMed |
  3. Nußbaumer B, Glechner A, Kaminski-Hartenthaler A, Mahlknecht P, Gartlehner G. Ezetimibe-Statin Combination Therapy. Dtsch Arztebl Int. 2016 Jul 1;113(26):445-53 | CrossRef | PubMed |
  4. Pandor A, Ara RM, Tumur I, Wilkinson AJ, Paisley S, Duenas A, et al. Ezetimibe monotherapy for cholesterol lowering in 2,722 people: systematic review and meta-analysis of randomized controlled trials. J Intern Med. 2009 May;265(5):568-80. | CrossRef | PubMed |
  5. Battaggia A, Donzelli A, Font M, Molteni D, Galvano A. Clinical efficacy and safety of Ezetimibe on major cardiovascular endpoints: systematic review and meta-analysis of randomized controlled trials. PLoS One. 2015 Apr 27;10(4):e0124587 | CrossRef | PubMed |
  6. Mikhailidis DP, Sibbring GC, Ballantyne CM, Davies GM, Catapano AL. Meta-analysis of the cholesterol-lowering effect of ezetimibe added to ongoing statin therapy. Curr Med Res Opin. 2007 Aug;23(8):2009-26 | PubMed |
  7. Santee J, Lindsey C, Pace H. Relative efficacy of antilipemic agents in non–high-density lipoprotein cholesterol reduction. J Pharm Pract. 2012 Aug;25(4):447-56 | PubMed |
  8. Mikhailidis DP, Lawson RW, McCormick AL, Sibbring GC, Tershakovec AM, Davies GM, et al. Comparative efficacy of the addition of ezetimibe to statin vs statin titration in patients with hypercholesterolaemia: systematic review and meta-analysis. Curr Med Res Opin. 2011 Jun;27(6):1191-210 | CrossRef | PubMed |
  9. Ambegaonkar BM, Tipping D, Polis AB, Tomassini JE, Tershakovec AM. Achieving goal lipid levels with ezetimibe plus statin add-on or switch therapy compared with doubling the statin dose. A pooled analysis. Atherosclerosis. 2014 Dec;237(2):829-37. | CrossRef | PubMed |
  10. Ara R, Tumur I, Pandor A, Duenas A, Williams R, Wilkinson A, et al. Ezetimibe for the treatment of hypercholesterolaemia: a systematic review and economic evaluation. Health Technol Assess. 2008 May;12(21):iii, xi-xiii, 1-212 | PubMed |
  11. Zieve F, Wenger NK, Ben-Yehuda O, Constance C, Bird S, Lee R, et al. Safety and efficacy of ezetimibe added to atorvastatin versus up titration of atorvastatin to 40 mg in Patients > or = 65 years of age (from the ZETia in the ELDerly [ZETELD] study). Am J Cardiol. 2010 Mar 1;105(5):656-63 | CrossRef | PubMed |
  12. Pearson TA, Denke MA, McBride PE, Battisti WP, Brady WE, Palmisano J. A community-based, randomized trial of ezetimibe added to statin therapy to attain NCEP ATP III goals for LDL cholesterol in hypercholesterolemic patients: the ezetimibe add-on to statin for effectiveness (EASE) trial. Mayo Clin Proc. 2005 May;80(5):587-95 | PubMed |
  13. Strony J, Yang B, Hanson ME, Veltri EP. Long-term safety and tolerability of ezetimibe coadministered with simvastatin in hypercholesterolemic patients: a randomized, 12-month double-blind extension study. Curr Med Res Opin. 2008 Nov;24(11):3149-57 | CrossRef | PubMed |
  14. Stein E, Stender S, Mata P, Sager P, Ponsonnet D, Melani L, et al. Achieving lipoprotein goals in patients at high risk with severe hypercholesterolemia: efficacy and safety of ezetimibe co-administered with atorvastatin. Am Heart J. 2004 Sep;148(3):447-55. | PubMed |
  15. Conard SE, Bays HE, Leiter LA, Bird SR, Rubino J, Lowe RS, et al. Efficacy and safety of ezetimibe added on to atorvastatin (20 mg) versus uptitration of atorvastatin (to 40 mg) in hypercholesterolemic patients at moderately high risk for coronary heart disease. Am J Cardiol. 2008 Dec 1;102(11):1489-94 | CrossRef | PubMed |
  16. Knopp RH, Gitter H, Truitt T, Bays H, Manion CV, Lipka LJ, et al. Effects of ezetimibe, a new cholesterol absorption inhibitor, on plasma lipids in patients with primary hypercholesterolemia. Eur Heart J. 2003 Apr;24(8):729-41 | PubMed |
  17. Goldberg RB, Guyton JR, Mazzone T, Weinstock RS, Polis A, Edwards P, et al. Ezetimibe/simvastatin vs atorvastatin in patients with type 2 diabetes mellitus and hypercholesterolemia: the VYTAL study. Mayo Clin Proc. 2006 Dec;81(12):1579-88. Erratum in: Mayo Clin Proc. 2007 Mar;82(3):387 | PubMed |
  18. Rodney RA, Sugimoto D, Wagman B, Zieve F, Kerzner B, Strony J, et al. Efficacy and safety of coadministration of ezetimibe and simvastatin in African-American patients with primary hypercholesterolemia. J Natl Med Assoc. 2006 May;98(5):772-8 | PubMed |
  19. Shankar PK, Bhat R, Prabhu M, Reddy BP, Reddy MS, Reddy M. Efficacy and tolerability of fixed-dose combination of simvastatin plus ezetimibe in patients with primary hypercholesterolemia: Results of a multicentric trial from India. J Clin Lipidol. 2007 Aug;1(4):264-70 | CrossRef | PubMed |
  20. Hing Ling PK, Civeira F, Dan AG, Hanson ME, Massaad R, De Tilleghem Cle B, et al. Ezetimibe/simvastatin 10/40 mg versus atorvastatin 40 mg in high cardiovascular risk patients with primary hypercholesterolemia: a randomized, double-blind, active-controlled, multicenter study. Lipids Health Dis. 2012 Jan 31;11:18 | CrossRef | PubMed |
  21. Piorkowski M, Fischer S, Stellbaum C, Jaster M, Martus P, Morguet AJ, et al. Treatment with ezetimibe plus low-dose atorvastatin compared with higher-dose atorvastatin alone: is sufficient cholesterol-lowering enough to inhibit platelets? J Am Coll Cardiol. 2007 Mar 13;49(10):1035-42 | PubMed |
  22. Nakamura T, Hirano M, Kitta Y, Fujioka D, Saito Y, Kawabata K, et al. A comparison of the efficacy of combined ezetimibe and statin therapy with doubling of statin dose in patients with remnant lipoproteinemia on previous statin therapy. J Cardiol. 2012 Jul;60(1):12-7 | CrossRef | PubMed |
  23. Davidson MH, McGarry T, Bettis R, Melani L, Lipka LJ, LeBeaut AP, et al. Ezetimibe coadministered with simvastatin in patients with primary hypercholesterolemia. J Am Coll Cardiol. 2002 Dec 18;40(12):2125-34 | PubMed |
  24. Melani L, Mills R, Hassman D, Lipetz R, Lipka L, LeBeaut A, et al. Efficacy and safety of ezetimibe coadministered with pravastatin in patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial. Eur Heart J. 2003 Apr;24(8):717-28 | PubMed |
  25. Meaney A, Ceballos G, Asbun J, Solache G, Mendoza E, Vela A, et al. The VYtorin on Carotid intima-media thickness and overall arterial rigidity (VYCTOR) study. J Clin Pharmacol. 2009 Jul;49(7):838-47 | CrossRef | PubMed |
  26. Blagden MD, Chipperfield R. Efficacy and safety of ezetimibe co-administered with atorvastatin in untreated patients with primary hypercholesterolaemia and coronary heart disease. Curr Med Res Opin. 2007 Apr;23(4):767-75 | PubMed |
  27. Masuda J, Tanigawa T, Yamada T, Nishimura Y, Sasou T, Nakata T, et al. Effect of combination therapy of ezetimibe and rosuvastatin on regression of coronary atherosclerosis in patients with coronary artery disease. Int Heart J. 2015 May 13;56(3):278-85 | CrossRef | PubMed |
  28. Masana L, Mata P, Gagné C, Sirah W, Cho M, Johnson-Levonas AO, et al. Long-term safety and, tolerability profiles and lipid-modifying efficacy of ezetimibe coadministered with ongoing simvastatin treatment: a multicenter, randomized, double-blind, placebo-controlled, 48-week extension study. Clin Ther. 2005 Feb;27(2):174-84 | CrossRef |
  29. Blazing MA, Giugliano RP, Cannon CP, Musliner TA, Tershakovec AM, White JA, et al. Evaluating cardiovascular event reduction with ezetimibe as an adjunct to simvastatin in 18,144 patients after acute coronary syndromes: final baseline characteristics of the IMPROVE-IT study population. Am Heart J. 2014 Aug;168(2):205-12.e1 | CrossRef | PubMed |
  30. Gaudiani LM, Lewin A, Meneghini L, Perevozskaya I, Plotkin D, Mitchel Y, et al. Efficacy and safety of ezetimibe co-administered with simvastatin in thiazolidinedione-treated type 2 diabetic patients. Diabetes Obes Metab. 2005 Jan;7(1):88-97 | PubMed |
  31. Landray M, Baigent C, Leaper C, Adu D, Altmann P, Armitage J, et al. The second United Kingdom Heart and Renal Protection (UK-HARP-II) Study: a randomized controlled study of the biochemical safety and efficacy of adding ezetimibe to simvastatin as initial therapy among patients with CKD. Am J Kidney Dis. 2006 Mar;47(3):385-95 | PubMed |
  32. Leiter LA, Bays H, Conard S, Bird S, Rubino J, Hanson ME, et al. Efficacy and safety of ezetimibe added on to atorvastatin (40 mg) compared with uptitration of atorvastatin (to 80 mg) in hypercholesterolemic patients at high risk of coronary heart disease. Am J Cardiol. 2008 Dec 1;102(11):1495-501 | CrossRef | PubMed |
  33. Kosoglou T, Statkevich P, Yang B, Suresh R, Zhu Y, Boutros T, et al. Pharmacodynamic interaction between ezetimibe and rosuvastatin. Curr Med Res Opin. 2004 Aug;20(8):1185-95 | PubMed |
  34. Kosoglou T, Statkevich P, Meyer I, Cutler DL, Musiol B, Yang B, et al. Effects of ezetimibe on the pharmacodynamics and pharmacokinetics of lovastatin. Curr Med Res Opin. 2004 Jun;20(6):955-65 | PubMed |
  35. Kosoglou T, Meyer I, Veltri EP, Statkevich P, Yang B, Zhu Y, et al. Pharmacodynamic interaction between the new selective cholesterol absorption inhibitor ezetimibe and simvastatin. Br J Clin Pharmacol. 2002 Sep;54(3):309-19 | PubMed |
  36. Kerzner B, Corbelli J, Sharp S, Lipka LJ, Melani L, LeBeaut A, et al. Efficacy and safety of ezetimibe coadministered with lovastatin in primary hypercholesterolemia. Am J Cardiol. 2003 Feb 15;91(4):418-24 | PubMed |
  37. Patel JV, Hughes EA. Efficacy, safety and LDL-C goal attainment of ezetimibe 10 mg-simvastatin 20 mg vs. placebo-simvastatin 20 mg in UK-based adults with coronary heart disease and hypercholesterolaemia. Int J Clin Pract. 2006 Aug;60(8):914-21 | PubMed |
  38. Guyton JR, Brown BG, Fazio S, Polis A, Tomassini JE, Tershakovec AM. Lipid-altering efficacy and safety of ezetimibe/simvastatin coadministered with extended-release niacin in patients with type IIa or type IIb hyperlipidemia. J Am Coll Cardiol. 2008 Apr 22;51(16):1564-72 | CrossRef | PubMed |
  39. Reckless JP, Henry P, Pomykaj T, Lim ST, Massaad R, Vandormael K, et al. Lipid-altering efficacy of ezetimibe/simvastatin 10/40 mg compared with doubling the statin dose in patients admitted to the hospital for a recent coronary event: the INFORCE study. Int J Clin Pract. 2008 Apr;62(4):539-54 | CrossRef | PubMed |
  40. McKenney JM, Jones PH, Bays HE, Knopp RH, Kashyap ML, Ruoff GE, et al. Comparative effects on lipid levels of combination therapy with a statin and extended-release niacin or ezetimibe versus a statin alone (the COMPELL study). Atherosclerosis. 2007 Jun;192(2):432-7 | PubMed |
  41. McKenney JM, Farnier M, Lo KW, Bays HE, Perevozkaya I, Carlson G, et al. Safety and efficacy of long-term co-administration of fenofibrate and ezetimibe in patients with mixed hyperlipidemia. J Am Coll Cardiol. 2006 Apr 18;47(8):1584-7 | PubMed |
  42. Cruz-Fernández JM, Bedarida GV, Adgey J, Allen C, Johnson-Levonas AO, Massaad R. Efficacy and safety of ezetimibe co-administered with ongoing atorvastatin therapy in achieving low-density lipoprotein goal in patients with hypercholesterolemia and coronary heart disease. Int J Clin Pract. 2005 Jun;59(6):619-27 | PubMed |
  43. Kastelein JJ, Akdim F, Stroes ES, Zwinderman AH, Bots ML, Stalenhoef AF, et al. Simvastatin with or without ezetimibe in familial hypercholesterolemia. N Engl J Med. 2008 Apr 3;358(14):1431-43. | PubMed |
  44. Rosen JB, Jimenez JG, Pirags V, Vides H, Hanson ME, Massaad R, et al. A comparison of efficacy and safety of an ezetimibe/simvastatin combination compared with other intensified lipid-lowering treatment strategies in diabetic patients with symptomatic cardiovascular disease. Diab Vasc Dis Res. 2013 May;10(3):277-86 | CrossRef | PubMed |
  45. Roeters van Lennep HW, Liem AH, Dunselman PH, Dallinga-Thie GM, Zwinderman AH, Jukema JW. The efficacy of statin monotherapy uptitration versus switching to ezetimibe/simvastatin: results of the EASEGO study. Curr Med Res Opin. 2008 Mar;24(3):685-94 | CrossRef | PubMed |
  46. Bays HE, Ose L, Fraser N, Tribble DL, Quinto K, Reyes R, et al. A multicenter, randomized, double-blind, placebo-controlled, factorial design study to evaluate the lipid-altering efficacy and safety profile of the ezetimibe/simvastatin tablet compared with ezetimibe and simvastatin monotherapy in patients with primary hypercholesterolemia. Clin Ther. 2004 Nov;26(11):1758-73 | PubMed |
  47. Bays HE, Davidson MH, Massaad R, Flaim D, Lowe RS, Tershakovec AM, et al. Safety and efficacy of ezetimibe added on to rosuvastatin 5 or 10 mg versus up-titration of rosuvastatin in patients with hypercholesterolemia (the ACTE Study). Am J Cardiol. 2011 Aug 15;108(4):523-30 | CrossRef | PubMed |
  48. Geiss HC, Otto C, Hund-Wissner E, Parhofer KG. Effects of ezetimibe on plasma lipoproteins in severely hypercholesterolemic patients treated with regular LDL-apheresis and statins. Atherosclerosis. 2005 May;180(1):107-12 | PubMed |
  49. Gouni-Berthold I, Berthold HK, Gylling H, Hallikainen M, Giannakidou E, Stier S, et al. Effects of ezetimibe and/or simvastatin on LDL receptor protein expression and on LDL receptor and HMG-CoA reductase gene expression: a randomized trial in healthy men. Atherosclerosis. 2008 May;198(1):198-207 | PubMed |
  50. Kouvelos GN, Arnaoutoglou EM, Matsagkas MI, Kostara C, Gartzonika C, Bairaktari ET, et al. Effects of rosuvastatin with or without ezetimibe on clinical outcomes in patients undergoing elective vascular surgery: results of a pilot study. J Cardiovasc Pharmacol Ther. 2013 Jan;18(1):5-12 | CrossRef | PubMed |
  51. Gagné C, Bays HE, Weiss SR, Mata P, Quinto K, Melino M, et al. Efficacy and safety of ezetimibe added to ongoing statin therapy for treatment of patients with primary hypercholesterolemia. Am J Cardiol. 2002 Nov 15;90(10):1084-91 | PubMed |
  52. Gagné C, Gaudet D, Bruckert E; Ezetimibe Study Group. Efficacy and safety of ezetimibe coadministered with atorvastatin or simvastatin in patients with homozygous familial hypercholesterolemia. Circulation. 2002 May 28;105(21):2469-75 | PubMed |
  53. Feldman T, Koren M, Insull W Jr, McKenney J, Schrott H, Lewin A, et al. Treatment of high-risk patients with ezetimibe plus simvastatin co-administration versus simvastatin alone to attain National Cholesterol Education Program Adult Treatment Panel III low-density lipoprotein cholesterol goals. Am J Cardiol. 2004 Jun 15;93(12):1481-6 | PubMed |
  54. Farnier M, Volpe M, Massaad R, Davies MJ, Allen C. Effect of co-administering ezetimibe with on-going simvastatin treatment on LDL-C goal attainment in hypercholesterolemic patients with coronary heart disease. Int J Cardiol. 2005 Jul 10;102(2):327-32 | PubMed |
  55. Farnier M, Roth E, Gil-Extremera B, Mendez GF, Macdonell G, Hamlin C, et al. Efficacy and safety of the coadministration of ezetimibe/simvastatin with fenofibrate in patients with mixed hyperlipidemia. Am Heart J. 2007 Feb;153(2):335.e1-8 | PubMed |
  56. Farnier M, Freeman MW, Macdonell G, Perevozskaya I, Davies MJ, Mitchel YB, et al. Efficacy and safety of the coadministration of ezetimibe with fenofibrate in patients with mixed hyperlipidaemia. Eur Heart J. 2005 May;26(9):897-905 | PubMed |
  57. Farnier M, Averna M, Missault L, Vaverkova H, Viigimaa M, Massaad R, et al. Lipid-altering efficacy of ezetimibe/simvastatin 10/20 mg compared with rosuvastatin 10 mg in high-risk hypercholesterolaemic patients inadequately controlled with prior statin monotherapy - The IN-CROSS study. Int J Clin Pract. 2009 Apr;63(4):547-59 | CrossRef | PubMed |
  58. Stein EA, Ballantyne CM, Windler E, Sirnes PA, Sussekov A, Yigit Z, et al. Efficacy and tolerability of fluvastatin XL 80 mg alone, ezetimibe alone, and the combination of fluvastatin XL 80 mg with ezetimibe in patients with a history of muscle-related side effects with other statins. Am J Cardiol. 2008 Feb 15;101(4):490-6 | CrossRef | PubMed |
  59. Dobs AS, Guyton JR, McClusky D, Ponsonnet D, Melani L, Lebeaut A (2003). Coadministration of ezetimibe with simvastatin. American College of Cardiology 52nd Annual Scientific Session, Chicago, Illinois (Published in: Journal of the American College of Cardiology. 2003;41(6, Supplement 1):227) | Link |
  60. Dagli N, Yavuzkir M, Karaca I. The effects of high dose pravastatin and low dose pravastatin and ezetimibe combination therapy on lipid, glucose metabolism and inflammation. Inflammation. 2007 Dec;30(6):230-5 | PubMed |
  61. Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P, et al. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. N Engl J Med. 2015 Jun 18;372(25):2387-97 | CrossRef | PubMed |
  62. Corp., M. S. & D. (2005). IMPROVE-IT: Examining Outcomes in Subjects With Acute Coronary Syndrome: Vytorin (Ezetimibe/Simvastatin) vs Simvastatin (P04103). Clinicaltrials.gov | Link |
  63. Constance C, Westphal S, Chung N, Lund M, McCrary Sisk C, Johnson-Levonas AO, et al. Efficacy of ezetimibe/simvastatin 10/20 and 10/40 mg compared with atorvastatin 20 mg in patients with type 2 diabetes mellitus. Diabetes Obes Metab. 2007 Jul;9(4):575-84 | PubMed |
  64. Ballantyne CM, Weiss R, Moccetti T, Vogt A, Eber B, Sosef F, et al. Efficacy and safety of rosuvastatin 40 mg alone or in combination with ezetimibe in patients at high risk of cardiovascular disease (results from the EXPLORER study). Am J Cardiol. 2007 Mar 1;99(5):673-80 | PubMed |
  65. Ballantyne CM, Blazing MA, King TR, Brady WE, Palmisano J. Efficacy and safety of ezetimibe co-administered with simvastatin compared with atorvastatin in adults with hypercholesterolemia. Am J Cardiol. 2004 Jun 15;93(12):1487-94. | PubMed |
  66. Ballantyne CM, Lipka LJ, Sager PT, Strony J, Alizadeh J, Suresh R, et al. Long-term safety and tolerability profile of ezetimibe and atorvastatin coadministration therapy in patients with primary hypercholesterolaemia. Int J Clin Pract. 2004 Jul;58(7):653-8 | PubMed |
  67. Ballantyne CM, Houri J, Notarbartolo A, Melani L, Lipka LJ, Suresh R, et al. Effect of ezetimibe coadministered with atorvastatin in 628 patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial. Circulation. 2003 May 20;107(19):2409-15 | PubMed |
  68. Ballantyne CM, Abate N, Yuan Z, King TR, Palmisano J. Dose-comparison study of the combination of ezetimibe and simvastatin (Vytorin) versus atorvastatin in patients with hypercholesterolemia: the Vytorin Versus Atorvastatin (VYVA) study. Am Heart J. 2005 Mar;149(3):464-73. Erratum in: Am Heart J. 2005 May;149(5):882. | PubMed |
  69. Chenot F, Montant PF, Marcovitch O, Blaimont M, de Meester A, Descamps OS. Co-administration of ezetimibe and simvastatin in acute myocardial infarction. Eur J Clin Invest. 2007 May;37(5):357-63 | PubMed |
  70. Dujovne CA, Ettinger MP, McNeer JF, Lipka LJ, LeBeaut AP, Suresh R, et al. Efficacy and safety of a potent new selective cholesterol absorption inhibitor, ezetimibe, in patients with primary hypercholesterolemia. Am J Cardiol. 2002 Nov 15;90(10):1092-7. Erratum in: Am J Cardiol. 2003 Jun 1;91(11):1399 | PubMed |
  71. Brohet C, Banai S, Alings AM, Massaad R, Davies MJ, Allen C. LDL-C goal attainment with the addition of ezetimibe to ongoing simvastatin treatment in coronary heart disease patients with hypercholesterolemia. Curr Med Res Opin. 2005 Apr;21(4):571-8 | PubMed |
  72. Barrios V, Amabile N, Paganelli F, Chen JW, Allen C, Johnson-Levonas AO, et al. Lipid-altering efficacy of switching from atorvastatin 10 mg/day to ezetimibe/simvastatin 10/20 mg/day compared to doubling the dose of atorvastatin in hypercholesterolaemic patients with atherosclerosis or coronary heart disease. Int J Clin Pract. 2005 Dec;59(12):1377-86 | PubMed |
  73. Baigent C, Landray MJ, Reith C, Emberson J, Wheeler DC, Tomson C, et al. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet. 2011 Jun 25;377(9784):2181-92 | CrossRef | PubMed |
  74. Arimura T, Miura S, Ike A, Sugihara M, Iwata A, Nishikawa H, et al. Comparison of the efficacy and safety of statin and statin/ezetimibe therapy after coronary stent implantation in patients with stable angina. J Cardiol. 2012 Aug;60(2):111-8 | CrossRef | PubMed |
  75. West AM, Anderson JD, Epstein FH, Meyer CH, Wang H, Hagspiel KD, et al. Low-density lipoprotein lowering does not improve calf muscle perfusion, energetics, or exercise performance in peripheral arterial disease. J Am Coll Cardiol. 2011 Aug 30;58(10):1068-76 | CrossRef | PubMed |
  76. West AM, Anderson JD, Meyer CH, Epstein FH, Wang H, Hagspiel KD, et al. The effect of ezetimibe on peripheral arterial atherosclerosis depends upon statin use at baseline. Atherosclerosis. 2011 Sep;218(1):156-62 | CrossRef | PubMed |
  77. Catapano AL, Davidson MH, Ballantyne CM, Brady WE, Gazzara RA, Tomassini JE, et al. Lipid-altering efficacy of the ezetimibe/simvastatin single tablet versus rosuvastatin in hypercholesterolemic patients. Curr Med Res Opin. 2006 Oct;22(10):2041-53 | PubMed |
  78. Goldberg AC, Sapre A, Liu J, Capece R, Mitchel YB; Ezetimibe Study Group. Efficacy and safety of ezetimibe coadministered with simvastatin in patients with primary hypercholesterolemia: a randomized, double-blind, placebo-controlled trial. Mayo Clin Proc. 2004 May;79(5):620-9 | PubMed |
  79. Rossebø AB, Pedersen TR, Boman K, Brudi P, Chambers JB, Egstrup K, et al. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N Engl J Med. 2008 Sep 25;359(13):1343-56 | CrossRef | PubMed |
  80. Roffi M, Patrono C, Collet JP, Mueller C, Valgimigli M, Andreotti F, et al. [2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC)]. G Ital Cardiol (Rome). 2016 Oct;17(10):831-872. | CrossRef | PubMed |
Chan DK, O'Rourke F, Shen Q, Mak JC, Hung WT. Meta-analysis of the cardiovascular benefits of intensive lipid lowering with statins. Acta Neurol Scand. 2011 Sep;124(3):188-95. | CrossRef | PubMed |

Sharma M, Ansari MT, Abou-Setta AM, Soares-Weiser K, Ooi TC, Sears M, et al. Systematic review: comparative effectiveness and harms of combination therapy and monotherapy for dyslipidemia. Ann Intern Med. 2009 Nov 3;151(9):622-30. | CrossRef | PubMed |

Nußbaumer B, Glechner A, Kaminski-Hartenthaler A, Mahlknecht P, Gartlehner G. Ezetimibe-Statin Combination Therapy. Dtsch Arztebl Int. 2016 Jul 1;113(26):445-53 | CrossRef | PubMed |

Pandor A, Ara RM, Tumur I, Wilkinson AJ, Paisley S, Duenas A, et al. Ezetimibe monotherapy for cholesterol lowering in 2,722 people: systematic review and meta-analysis of randomized controlled trials. J Intern Med. 2009 May;265(5):568-80. | CrossRef | PubMed |

Battaggia A, Donzelli A, Font M, Molteni D, Galvano A. Clinical efficacy and safety of Ezetimibe on major cardiovascular endpoints: systematic review and meta-analysis of randomized controlled trials. PLoS One. 2015 Apr 27;10(4):e0124587 | CrossRef | PubMed |

Mikhailidis DP, Sibbring GC, Ballantyne CM, Davies GM, Catapano AL. Meta-analysis of the cholesterol-lowering effect of ezetimibe added to ongoing statin therapy. Curr Med Res Opin. 2007 Aug;23(8):2009-26 | PubMed |

Santee J, Lindsey C, Pace H. Relative efficacy of antilipemic agents in non–high-density lipoprotein cholesterol reduction. J Pharm Pract. 2012 Aug;25(4):447-56 | PubMed |

Mikhailidis DP, Lawson RW, McCormick AL, Sibbring GC, Tershakovec AM, Davies GM, et al. Comparative efficacy of the addition of ezetimibe to statin vs statin titration in patients with hypercholesterolaemia: systematic review and meta-analysis. Curr Med Res Opin. 2011 Jun;27(6):1191-210 | CrossRef | PubMed |

Ambegaonkar BM, Tipping D, Polis AB, Tomassini JE, Tershakovec AM. Achieving goal lipid levels with ezetimibe plus statin add-on or switch therapy compared with doubling the statin dose. A pooled analysis. Atherosclerosis. 2014 Dec;237(2):829-37. | CrossRef | PubMed |

Ara R, Tumur I, Pandor A, Duenas A, Williams R, Wilkinson A, et al. Ezetimibe for the treatment of hypercholesterolaemia: a systematic review and economic evaluation. Health Technol Assess. 2008 May;12(21):iii, xi-xiii, 1-212 | PubMed |

Zieve F, Wenger NK, Ben-Yehuda O, Constance C, Bird S, Lee R, et al. Safety and efficacy of ezetimibe added to atorvastatin versus up titration of atorvastatin to 40 mg in Patients > or = 65 years of age (from the ZETia in the ELDerly [ZETELD] study). Am J Cardiol. 2010 Mar 1;105(5):656-63 | CrossRef | PubMed |

Pearson TA, Denke MA, McBride PE, Battisti WP, Brady WE, Palmisano J. A community-based, randomized trial of ezetimibe added to statin therapy to attain NCEP ATP III goals for LDL cholesterol in hypercholesterolemic patients: the ezetimibe add-on to statin for effectiveness (EASE) trial. Mayo Clin Proc. 2005 May;80(5):587-95 | PubMed |

Strony J, Yang B, Hanson ME, Veltri EP. Long-term safety and tolerability of ezetimibe coadministered with simvastatin in hypercholesterolemic patients: a randomized, 12-month double-blind extension study. Curr Med Res Opin. 2008 Nov;24(11):3149-57 | CrossRef | PubMed |

Stein E, Stender S, Mata P, Sager P, Ponsonnet D, Melani L, et al. Achieving lipoprotein goals in patients at high risk with severe hypercholesterolemia: efficacy and safety of ezetimibe co-administered with atorvastatin. Am Heart J. 2004 Sep;148(3):447-55. | PubMed |

Conard SE, Bays HE, Leiter LA, Bird SR, Rubino J, Lowe RS, et al. Efficacy and safety of ezetimibe added on to atorvastatin (20 mg) versus uptitration of atorvastatin (to 40 mg) in hypercholesterolemic patients at moderately high risk for coronary heart disease. Am J Cardiol. 2008 Dec 1;102(11):1489-94 | CrossRef | PubMed |

Knopp RH, Gitter H, Truitt T, Bays H, Manion CV, Lipka LJ, et al. Effects of ezetimibe, a new cholesterol absorption inhibitor, on plasma lipids in patients with primary hypercholesterolemia. Eur Heart J. 2003 Apr;24(8):729-41 | PubMed |

Goldberg RB, Guyton JR, Mazzone T, Weinstock RS, Polis A, Edwards P, et al. Ezetimibe/simvastatin vs atorvastatin in patients with type 2 diabetes mellitus and hypercholesterolemia: the VYTAL study. Mayo Clin Proc. 2006 Dec;81(12):1579-88. Erratum in: Mayo Clin Proc. 2007 Mar;82(3):387 | PubMed |

Rodney RA, Sugimoto D, Wagman B, Zieve F, Kerzner B, Strony J, et al. Efficacy and safety of coadministration of ezetimibe and simvastatin in African-American patients with primary hypercholesterolemia. J Natl Med Assoc. 2006 May;98(5):772-8 | PubMed |

Shankar PK, Bhat R, Prabhu M, Reddy BP, Reddy MS, Reddy M. Efficacy and tolerability of fixed-dose combination of simvastatin plus ezetimibe in patients with primary hypercholesterolemia: Results of a multicentric trial from India. J Clin Lipidol. 2007 Aug;1(4):264-70 | CrossRef | PubMed |

Hing Ling PK, Civeira F, Dan AG, Hanson ME, Massaad R, De Tilleghem Cle B, et al. Ezetimibe/simvastatin 10/40 mg versus atorvastatin 40 mg in high cardiovascular risk patients with primary hypercholesterolemia: a randomized, double-blind, active-controlled, multicenter study. Lipids Health Dis. 2012 Jan 31;11:18 | CrossRef | PubMed |

Piorkowski M, Fischer S, Stellbaum C, Jaster M, Martus P, Morguet AJ, et al. Treatment with ezetimibe plus low-dose atorvastatin compared with higher-dose atorvastatin alone: is sufficient cholesterol-lowering enough to inhibit platelets? J Am Coll Cardiol. 2007 Mar 13;49(10):1035-42 | PubMed |

Nakamura T, Hirano M, Kitta Y, Fujioka D, Saito Y, Kawabata K, et al. A comparison of the efficacy of combined ezetimibe and statin therapy with doubling of statin dose in patients with remnant lipoproteinemia on previous statin therapy. J Cardiol. 2012 Jul;60(1):12-7 | CrossRef | PubMed |

Davidson MH, McGarry T, Bettis R, Melani L, Lipka LJ, LeBeaut AP, et al. Ezetimibe coadministered with simvastatin in patients with primary hypercholesterolemia. J Am Coll Cardiol. 2002 Dec 18;40(12):2125-34 | PubMed |

Melani L, Mills R, Hassman D, Lipetz R, Lipka L, LeBeaut A, et al. Efficacy and safety of ezetimibe coadministered with pravastatin in patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial. Eur Heart J. 2003 Apr;24(8):717-28 | PubMed |

Meaney A, Ceballos G, Asbun J, Solache G, Mendoza E, Vela A, et al. The VYtorin on Carotid intima-media thickness and overall arterial rigidity (VYCTOR) study. J Clin Pharmacol. 2009 Jul;49(7):838-47 | CrossRef | PubMed |

Blagden MD, Chipperfield R. Efficacy and safety of ezetimibe co-administered with atorvastatin in untreated patients with primary hypercholesterolaemia and coronary heart disease. Curr Med Res Opin. 2007 Apr;23(4):767-75 | PubMed |

Masuda J, Tanigawa T, Yamada T, Nishimura Y, Sasou T, Nakata T, et al. Effect of combination therapy of ezetimibe and rosuvastatin on regression of coronary atherosclerosis in patients with coronary artery disease. Int Heart J. 2015 May 13;56(3):278-85 | CrossRef | PubMed |

Masana L, Mata P, Gagné C, Sirah W, Cho M, Johnson-Levonas AO, et al. Long-term safety and, tolerability profiles and lipid-modifying efficacy of ezetimibe coadministered with ongoing simvastatin treatment: a multicenter, randomized, double-blind, placebo-controlled, 48-week extension study. Clin Ther. 2005 Feb;27(2):174-84 | CrossRef |

Blazing MA, Giugliano RP, Cannon CP, Musliner TA, Tershakovec AM, White JA, et al. Evaluating cardiovascular event reduction with ezetimibe as an adjunct to simvastatin in 18,144 patients after acute coronary syndromes: final baseline characteristics of the IMPROVE-IT study population. Am Heart J. 2014 Aug;168(2):205-12.e1 | CrossRef | PubMed |

Gaudiani LM, Lewin A, Meneghini L, Perevozskaya I, Plotkin D, Mitchel Y, et al. Efficacy and safety of ezetimibe co-administered with simvastatin in thiazolidinedione-treated type 2 diabetic patients. Diabetes Obes Metab. 2005 Jan;7(1):88-97 | PubMed |

Landray M, Baigent C, Leaper C, Adu D, Altmann P, Armitage J, et al. The second United Kingdom Heart and Renal Protection (UK-HARP-II) Study: a randomized controlled study of the biochemical safety and efficacy of adding ezetimibe to simvastatin as initial therapy among patients with CKD. Am J Kidney Dis. 2006 Mar;47(3):385-95 | PubMed |

Leiter LA, Bays H, Conard S, Bird S, Rubino J, Hanson ME, et al. Efficacy and safety of ezetimibe added on to atorvastatin (40 mg) compared with uptitration of atorvastatin (to 80 mg) in hypercholesterolemic patients at high risk of coronary heart disease. Am J Cardiol. 2008 Dec 1;102(11):1495-501 | CrossRef | PubMed |

Kosoglou T, Statkevich P, Yang B, Suresh R, Zhu Y, Boutros T, et al. Pharmacodynamic interaction between ezetimibe and rosuvastatin. Curr Med Res Opin. 2004 Aug;20(8):1185-95 | PubMed |

Kosoglou T, Statkevich P, Meyer I, Cutler DL, Musiol B, Yang B, et al. Effects of ezetimibe on the pharmacodynamics and pharmacokinetics of lovastatin. Curr Med Res Opin. 2004 Jun;20(6):955-65 | PubMed |

Kosoglou T, Meyer I, Veltri EP, Statkevich P, Yang B, Zhu Y, et al. Pharmacodynamic interaction between the new selective cholesterol absorption inhibitor ezetimibe and simvastatin. Br J Clin Pharmacol. 2002 Sep;54(3):309-19 | PubMed |

Kerzner B, Corbelli J, Sharp S, Lipka LJ, Melani L, LeBeaut A, et al. Efficacy and safety of ezetimibe coadministered with lovastatin in primary hypercholesterolemia. Am J Cardiol. 2003 Feb 15;91(4):418-24 | PubMed |

Patel JV, Hughes EA. Efficacy, safety and LDL-C goal attainment of ezetimibe 10 mg-simvastatin 20 mg vs. placebo-simvastatin 20 mg in UK-based adults with coronary heart disease and hypercholesterolaemia. Int J Clin Pract. 2006 Aug;60(8):914-21 | PubMed |

Guyton JR, Brown BG, Fazio S, Polis A, Tomassini JE, Tershakovec AM. Lipid-altering efficacy and safety of ezetimibe/simvastatin coadministered with extended-release niacin in patients with type IIa or type IIb hyperlipidemia. J Am Coll Cardiol. 2008 Apr 22;51(16):1564-72 | CrossRef | PubMed |

Reckless JP, Henry P, Pomykaj T, Lim ST, Massaad R, Vandormael K, et al. Lipid-altering efficacy of ezetimibe/simvastatin 10/40 mg compared with doubling the statin dose in patients admitted to the hospital for a recent coronary event: the INFORCE study. Int J Clin Pract. 2008 Apr;62(4):539-54 | CrossRef | PubMed |

McKenney JM, Jones PH, Bays HE, Knopp RH, Kashyap ML, Ruoff GE, et al. Comparative effects on lipid levels of combination therapy with a statin and extended-release niacin or ezetimibe versus a statin alone (the COMPELL study). Atherosclerosis. 2007 Jun;192(2):432-7 | PubMed |

McKenney JM, Farnier M, Lo KW, Bays HE, Perevozkaya I, Carlson G, et al. Safety and efficacy of long-term co-administration of fenofibrate and ezetimibe in patients with mixed hyperlipidemia. J Am Coll Cardiol. 2006 Apr 18;47(8):1584-7 | PubMed |

Cruz-Fernández JM, Bedarida GV, Adgey J, Allen C, Johnson-Levonas AO, Massaad R. Efficacy and safety of ezetimibe co-administered with ongoing atorvastatin therapy in achieving low-density lipoprotein goal in patients with hypercholesterolemia and coronary heart disease. Int J Clin Pract. 2005 Jun;59(6):619-27 | PubMed |

Kastelein JJ, Akdim F, Stroes ES, Zwinderman AH, Bots ML, Stalenhoef AF, et al. Simvastatin with or without ezetimibe in familial hypercholesterolemia. N Engl J Med. 2008 Apr 3;358(14):1431-43. | PubMed |

Rosen JB, Jimenez JG, Pirags V, Vides H, Hanson ME, Massaad R, et al. A comparison of efficacy and safety of an ezetimibe/simvastatin combination compared with other intensified lipid-lowering treatment strategies in diabetic patients with symptomatic cardiovascular disease. Diab Vasc Dis Res. 2013 May;10(3):277-86 | CrossRef | PubMed |

Roeters van Lennep HW, Liem AH, Dunselman PH, Dallinga-Thie GM, Zwinderman AH, Jukema JW. The efficacy of statin monotherapy uptitration versus switching to ezetimibe/simvastatin: results of the EASEGO study. Curr Med Res Opin. 2008 Mar;24(3):685-94 | CrossRef | PubMed |

Bays HE, Ose L, Fraser N, Tribble DL, Quinto K, Reyes R, et al. A multicenter, randomized, double-blind, placebo-controlled, factorial design study to evaluate the lipid-altering efficacy and safety profile of the ezetimibe/simvastatin tablet compared with ezetimibe and simvastatin monotherapy in patients with primary hypercholesterolemia. Clin Ther. 2004 Nov;26(11):1758-73 | PubMed |

Bays HE, Davidson MH, Massaad R, Flaim D, Lowe RS, Tershakovec AM, et al. Safety and efficacy of ezetimibe added on to rosuvastatin 5 or 10 mg versus up-titration of rosuvastatin in patients with hypercholesterolemia (the ACTE Study). Am J Cardiol. 2011 Aug 15;108(4):523-30 | CrossRef | PubMed |

Geiss HC, Otto C, Hund-Wissner E, Parhofer KG. Effects of ezetimibe on plasma lipoproteins in severely hypercholesterolemic patients treated with regular LDL-apheresis and statins. Atherosclerosis. 2005 May;180(1):107-12 | PubMed |

Gouni-Berthold I, Berthold HK, Gylling H, Hallikainen M, Giannakidou E, Stier S, et al. Effects of ezetimibe and/or simvastatin on LDL receptor protein expression and on LDL receptor and HMG-CoA reductase gene expression: a randomized trial in healthy men. Atherosclerosis. 2008 May;198(1):198-207 | PubMed |

Kouvelos GN, Arnaoutoglou EM, Matsagkas MI, Kostara C, Gartzonika C, Bairaktari ET, et al. Effects of rosuvastatin with or without ezetimibe on clinical outcomes in patients undergoing elective vascular surgery: results of a pilot study. J Cardiovasc Pharmacol Ther. 2013 Jan;18(1):5-12 | CrossRef | PubMed |

Gagné C, Bays HE, Weiss SR, Mata P, Quinto K, Melino M, et al. Efficacy and safety of ezetimibe added to ongoing statin therapy for treatment of patients with primary hypercholesterolemia. Am J Cardiol. 2002 Nov 15;90(10):1084-91 | PubMed |

Gagné C, Gaudet D, Bruckert E; Ezetimibe Study Group. Efficacy and safety of ezetimibe coadministered with atorvastatin or simvastatin in patients with homozygous familial hypercholesterolemia. Circulation. 2002 May 28;105(21):2469-75 | PubMed |

Feldman T, Koren M, Insull W Jr, McKenney J, Schrott H, Lewin A, et al. Treatment of high-risk patients with ezetimibe plus simvastatin co-administration versus simvastatin alone to attain National Cholesterol Education Program Adult Treatment Panel III low-density lipoprotein cholesterol goals. Am J Cardiol. 2004 Jun 15;93(12):1481-6 | PubMed |

Farnier M, Volpe M, Massaad R, Davies MJ, Allen C. Effect of co-administering ezetimibe with on-going simvastatin treatment on LDL-C goal attainment in hypercholesterolemic patients with coronary heart disease. Int J Cardiol. 2005 Jul 10;102(2):327-32 | PubMed |

Farnier M, Roth E, Gil-Extremera B, Mendez GF, Macdonell G, Hamlin C, et al. Efficacy and safety of the coadministration of ezetimibe/simvastatin with fenofibrate in patients with mixed hyperlipidemia. Am Heart J. 2007 Feb;153(2):335.e1-8 | PubMed |

Farnier M, Freeman MW, Macdonell G, Perevozskaya I, Davies MJ, Mitchel YB, et al. Efficacy and safety of the coadministration of ezetimibe with fenofibrate in patients with mixed hyperlipidaemia. Eur Heart J. 2005 May;26(9):897-905 | PubMed |

Farnier M, Averna M, Missault L, Vaverkova H, Viigimaa M, Massaad R, et al. Lipid-altering efficacy of ezetimibe/simvastatin 10/20 mg compared with rosuvastatin 10 mg in high-risk hypercholesterolaemic patients inadequately controlled with prior statin monotherapy - The IN-CROSS study. Int J Clin Pract. 2009 Apr;63(4):547-59 | CrossRef | PubMed |

Stein EA, Ballantyne CM, Windler E, Sirnes PA, Sussekov A, Yigit Z, et al. Efficacy and tolerability of fluvastatin XL 80 mg alone, ezetimibe alone, and the combination of fluvastatin XL 80 mg with ezetimibe in patients with a history of muscle-related side effects with other statins. Am J Cardiol. 2008 Feb 15;101(4):490-6 | CrossRef | PubMed |

Dobs AS, Guyton JR, McClusky D, Ponsonnet D, Melani L, Lebeaut A (2003). Coadministration of ezetimibe with simvastatin. American College of Cardiology 52nd Annual Scientific Session, Chicago, Illinois (Published in: Journal of the American College of Cardiology. 2003;41(6, Supplement 1):227) | Link |

Dagli N, Yavuzkir M, Karaca I. The effects of high dose pravastatin and low dose pravastatin and ezetimibe combination therapy on lipid, glucose metabolism and inflammation. Inflammation. 2007 Dec;30(6):230-5 | PubMed |

Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P, et al. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. N Engl J Med. 2015 Jun 18;372(25):2387-97 | CrossRef | PubMed |

Corp., M. S. & D. (2005). IMPROVE-IT: Examining Outcomes in Subjects With Acute Coronary Syndrome: Vytorin (Ezetimibe/Simvastatin) vs Simvastatin (P04103). Clinicaltrials.gov | Link |

Constance C, Westphal S, Chung N, Lund M, McCrary Sisk C, Johnson-Levonas AO, et al. Efficacy of ezetimibe/simvastatin 10/20 and 10/40 mg compared with atorvastatin 20 mg in patients with type 2 diabetes mellitus. Diabetes Obes Metab. 2007 Jul;9(4):575-84 | PubMed |

Ballantyne CM, Weiss R, Moccetti T, Vogt A, Eber B, Sosef F, et al. Efficacy and safety of rosuvastatin 40 mg alone or in combination with ezetimibe in patients at high risk of cardiovascular disease (results from the EXPLORER study). Am J Cardiol. 2007 Mar 1;99(5):673-80 | PubMed |

Ballantyne CM, Blazing MA, King TR, Brady WE, Palmisano J. Efficacy and safety of ezetimibe co-administered with simvastatin compared with atorvastatin in adults with hypercholesterolemia. Am J Cardiol. 2004 Jun 15;93(12):1487-94. | PubMed |

Ballantyne CM, Lipka LJ, Sager PT, Strony J, Alizadeh J, Suresh R, et al. Long-term safety and tolerability profile of ezetimibe and atorvastatin coadministration therapy in patients with primary hypercholesterolaemia. Int J Clin Pract. 2004 Jul;58(7):653-8 | PubMed |

Ballantyne CM, Houri J, Notarbartolo A, Melani L, Lipka LJ, Suresh R, et al. Effect of ezetimibe coadministered with atorvastatin in 628 patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial. Circulation. 2003 May 20;107(19):2409-15 | PubMed |

Ballantyne CM, Abate N, Yuan Z, King TR, Palmisano J. Dose-comparison study of the combination of ezetimibe and simvastatin (Vytorin) versus atorvastatin in patients with hypercholesterolemia: the Vytorin Versus Atorvastatin (VYVA) study. Am Heart J. 2005 Mar;149(3):464-73. Erratum in: Am Heart J. 2005 May;149(5):882. | PubMed |

Chenot F, Montant PF, Marcovitch O, Blaimont M, de Meester A, Descamps OS. Co-administration of ezetimibe and simvastatin in acute myocardial infarction. Eur J Clin Invest. 2007 May;37(5):357-63 | PubMed |

Dujovne CA, Ettinger MP, McNeer JF, Lipka LJ, LeBeaut AP, Suresh R, et al. Efficacy and safety of a potent new selective cholesterol absorption inhibitor, ezetimibe, in patients with primary hypercholesterolemia. Am J Cardiol. 2002 Nov 15;90(10):1092-7. Erratum in: Am J Cardiol. 2003 Jun 1;91(11):1399 | PubMed |

Brohet C, Banai S, Alings AM, Massaad R, Davies MJ, Allen C. LDL-C goal attainment with the addition of ezetimibe to ongoing simvastatin treatment in coronary heart disease patients with hypercholesterolemia. Curr Med Res Opin. 2005 Apr;21(4):571-8 | PubMed |

Barrios V, Amabile N, Paganelli F, Chen JW, Allen C, Johnson-Levonas AO, et al. Lipid-altering efficacy of switching from atorvastatin 10 mg/day to ezetimibe/simvastatin 10/20 mg/day compared to doubling the dose of atorvastatin in hypercholesterolaemic patients with atherosclerosis or coronary heart disease. Int J Clin Pract. 2005 Dec;59(12):1377-86 | PubMed |

Baigent C, Landray MJ, Reith C, Emberson J, Wheeler DC, Tomson C, et al. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet. 2011 Jun 25;377(9784):2181-92 | CrossRef | PubMed |

Arimura T, Miura S, Ike A, Sugihara M, Iwata A, Nishikawa H, et al. Comparison of the efficacy and safety of statin and statin/ezetimibe therapy after coronary stent implantation in patients with stable angina. J Cardiol. 2012 Aug;60(2):111-8 | CrossRef | PubMed |

West AM, Anderson JD, Epstein FH, Meyer CH, Wang H, Hagspiel KD, et al. Low-density lipoprotein lowering does not improve calf muscle perfusion, energetics, or exercise performance in peripheral arterial disease. J Am Coll Cardiol. 2011 Aug 30;58(10):1068-76 | CrossRef | PubMed |

West AM, Anderson JD, Meyer CH, Epstein FH, Wang H, Hagspiel KD, et al. The effect of ezetimibe on peripheral arterial atherosclerosis depends upon statin use at baseline. Atherosclerosis. 2011 Sep;218(1):156-62 | CrossRef | PubMed |

Catapano AL, Davidson MH, Ballantyne CM, Brady WE, Gazzara RA, Tomassini JE, et al. Lipid-altering efficacy of the ezetimibe/simvastatin single tablet versus rosuvastatin in hypercholesterolemic patients. Curr Med Res Opin. 2006 Oct;22(10):2041-53 | PubMed |

Goldberg AC, Sapre A, Liu J, Capece R, Mitchel YB; Ezetimibe Study Group. Efficacy and safety of ezetimibe coadministered with simvastatin in patients with primary hypercholesterolemia: a randomized, double-blind, placebo-controlled trial. Mayo Clin Proc. 2004 May;79(5):620-9 | PubMed |

Rossebø AB, Pedersen TR, Boman K, Brudi P, Chambers JB, Egstrup K, et al. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N Engl J Med. 2008 Sep 25;359(13):1343-56 | CrossRef | PubMed |

Roffi M, Patrono C, Collet JP, Mueller C, Valgimigli M, Andreotti F, et al. [2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC)]. G Ital Cardiol (Rome). 2016 Oct;17(10):831-872. | CrossRef | PubMed |

Edición Julio 2022
icon Estudios originales
Caracterización clínica, psicológica y sociofamiliar de la conducta suicida en adolescentes chilenos: análisis de correspondencias múltiples

Asociación de biomarcadores y severidad de COVID-19: estudio transversal

Sistematización de iniciativas en salud sexual y reproductiva según criterios de buenas prácticas en repuesta a la pandemia COVID-19 en la atención primaria en Chile

NUEVO SISTEMA EDITORIAL
Autores
Abrir sesión
Registro
Recibir alertas
Politica de cobros
Políticas editoriales
Instrucciones para autores
Equipo editorial
Comité editorial
¿Desea ser revisor?
Contactos y soporte
rssFacebookTwitter
ISSN 0717-6384